Host genetic variants and hepatitis B virologic features in HBeAg-negative hepatitis B carriers with long-term biochemical remission

Purpose: A significant portion of HBeAg-negative chronic hepatitis B patients have persistently normal serum alanine aminotransferase levels (PNALT). We thus investigated host genetic variants and virological features in HBeAg-negative hepatitis B carriers.

Methods: Baseline clinical and virological features of 133 HBeAg-negative hepatitis B carriers (77 with PNALT and 56 with chronic hepatitis activity) with follow-up for more than 5 years were investigated. Three single nucleotide polymorphisms (SNPs) located within or around human leukocyte antigen (HLA)-DPA1, HLA-DPB1, and interleukin (IL) 28B loci were genotyped.

Results: The genotype frequencies of these SNPs were comparable between hepatitis B carriers with PNALT and those with chronic hepatitis. Compared with hepatitis B carriers with PNALT, those with chronic hepatitis had significantly higher baseline serum HBV-DNA levels (4.96 vs. 4.04 log10 IU/ml, P = 0.001). Baseline serum HBV-DNA level > 2000 IU/ml (OR, 8.42; 95% CI, 2.74-25.90, P < 0.001) were the only independent factor associated with chronic hepatitis activity. Changes of serum HBV-DNA in 30 hepatitis B carriers with PNALT had showed a significant reduction of viral load from baseline to last visit (mean difference of paired HBV-DNA levels: -0.78 log10 IU/ml, 95% CI: -1.57 to -0.013, P = 0.047). In contrast, no significant reduction of viral load was found in 28 patients with chronic hepatitis.

Conclusions: The results indicate that lower baseline serum HBV-DNA level and viral load reduction over time are associated with long-term biochemical remission in HBeAg-negative hepatitis B carriers.